Project Summary Influenza infection causes thousands of deaths each year, largely among older adults (?65 yrs). Although annual vaccination is recommended to prevent these deaths, vaccine effectiveness and Thus, there is a critical need to enhance vaccine responses in older adults through adjuvants that are cost-effective and free of debilitating side effects. Localized resistance exercise immediately prior to inoculation has been shown to enhance vaccine responses among young adults, but this has not been examined in older adults. Further, it has not been established if the adjuvant effect of exercise is due to a local immune response in the targeted muscle or if it is a systemic response, as only the inoculated arm has been targeted by exercise. Finally, it is important to identify older adults most likely to have impaired vaccine responses, who accordingly may receive the most benefit from exercise. Cytomegalovirus (CMV) is present in most older adults, either as a latent or chronic infection. Chronic CMV infection can indicate compromised immunity and so may be predictive of decreased vaccine immunity. We propose to determine whether a single bout of resistance exercise can enhance vaccine responses to the the aging immune system reduces leaves older adults vulnerable to infection. seasonal influenza vaccine in older adults. This project will also shed light on whether the exercise-effect is local or systemic, and help characterize those older adults most likely to benefit from exercise prior to vaccination. Community dwelling non-frail older adults unaccustomed to resistance exercise (n=100) will be randomized to 1 of 3 groups: exercise in the inoculated arm, exercise in the non-inoculated arm, and resting control (standard of care). Exercise groups will perform resistance exercise targeting the deltoid and biceps bracchi immediately prior to receiving the influenza vaccine; the control group will rest quietly. The exercise will be calibrated to the ability of each individual. Antibody titer, cell mediated immune responses (CMI), and seroprotection rates will be assessed prior to and at various points (peak and residual responses) after vaccination. Vaccine responses will be compared between the three groups and between participants with chronic or latent CMV infection. We will control for participants' sex, age, and initial antibody titer (pre- vaccination). We hypothesize that exercise of the inoculated arm will increase vaccine responses compared to exercise of the non-inoculated arm and rest. We further hypothesize that participants with chronic CMV infection will have poorer vaccine responses compared to participants with latent CMV infection, and that exercise will have the largest adjuvant effect in this group. These experiments will demonstrate whether resistance exercise can be used as a simple, inexpensive, and practical vaccine adjuvant in community dwelling non-frail older adults.